Polymorphisms in cytotoxic T-lymphocyte associated antigen 4 gene does not affect scytotoxic T-lymphocyte associated antigen 4 levels in human papillomavirus-infected women with or without cervical cancer

Background: Cervical cancer (CaCx) is the second most common cancer in Indian women. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) + 49 AA polymorphism is known to be associated with CaCx. Current attempt is to use immunotherapy for the treatment of metastatic melanoma and metastatic castration-resistant prostate cancer, i.e., blocking of CTLA-4 using a fully human monoclonal CTLA-4 antibody to disrupt its inhibitory signal. This allows the CTLs to destroy the cancer cells. There is no information available on the soluble level of CTLA-4 on which the immunotherapy is targeted. This is specifically in Indian population including cases with CaCx. Objective: The aim of this study is to evaluate the levels of soluble CTLA-4 (sCTLA-4) in human papillomavirus (HPV)-infected women with or without CaCx and their association with the polymorphism at CTLA-4 + 49 A/G and CTLA-4 ?318 C/T genotypes. Materials and Methods: This is an exploratory case–control study involving two groups of HPV-infected women, the cases were with invasive CaCx and the control group was women with the healthy cervix. sCTLA-4 levels were measured using ELISA in 92 CaCx cases and 57 HPV-positive women with the healthy cervix. Results: Both cases and controls have similar sCTLA-4 levels. Comparison of CTLA-4 + 49A/G and ?318 C/T genotypes with sCTLA-4 levels among cases and control also did not show any statistically significant difference. Conclusion: The present study suggests sCTLA-4 levels are not affected by a polymorphism at + 49 A>G CTLA-4. Hence, levels of CTLA-4 are similar in both CaCx cases and control group.

Current evidence and the evolving role of sunitinib in the management of renal cell carcinoma.

The development of targeted agents has expanded the anticancer arsenal available to oncologists and revolutionized the field of cancer treatment. In patients with advanced renal cell carcinoma (RCC), small molecule targeted therapies have improved clinical outcomes compared with cytokine‑based treatments. Sunitinib malate is one such drug that has demonstrated clinical efficacy in patients with metastatic renal cell carcinoma (mRCC). This oral, multi‑targeted tyrosine kinase inhibitor is approved for use in multiple countries for the treatment of advanced RCC and gastrointestinal stromal tumor patients who have progressed on imatinib therapy. In patients with advanced RCC, sunitinib significantly improves clinical outcomes with a favorable safety profile compared with conventional treatment with interferon‑a. The clinically proven treatment and safety outcomes have led investigators to evaluate the merits of sunitinib therapy in the adjuvant and neoadjuvant setting in patients with mRCC. In the neoadjuvant setting, preliminary data suggest that sunitinib can effectively reduce the primary tumor and facilitate surgical resection in patients with locally advanced and mRCC. Post‑operative complications were observed in some patients, but the overall safety profile and efficacy suggests that mRCC patients with surgically inoperable tumors may benefit from neoadjuvant sunitinib therapy. Ongoing clinical trials should provide insight into the value of sunitinib as adjuvant therapy.

Uterine smooth muscle tumors of uncertain malignant potential and atypical leiomyoma: A morphological study of these grey zones with clinical correlation.

Objectives: To study the histological features in uterine STUMP, and atypical leiomyomas (AL), and to correlate with clinical outcome. Materials and Methods: From January 2004 to August 2010, a total of 21 cases were retrieved from records, labeled as STUMP(7), AL (5), AL with low risk of recurrence (2), smooth muscle tumor of low malignant potential (STLMP) (2), and symplastic leiomyoma (5). The slides were reviewed for coagulative tumor cell necrosis (CTCN), hyaline necrosis/ infarction type necrosis, presence and degree of cytological atypia, mitotic activity, epithelioid morphology and myxoid features. The other characteristics (such as size, circumscription, individual tumor cell necrosis), were noted, wherever available. Results: The mean age was 45 years (median 46; range 24-67 yrs). CTCN was seen in 2 cases on examination of additional material; wherein a revised diagnosis of leiomyosarcoma had been given. Infarction type necrosis and individual cell necrosis was seen in 2 and 3 cases, respectively. Mitoses were less than 5/10hpf in all the cases. One of the tumours labeled as STUMP also had concurrent endometrial adenocarcinoma. Follow up: Follow-up was available in 11 cases (52.3%). One patient had died. (cause not known). In 10 patients, the follow-up ranged from 4 to 56 months (mean 20.9 months; median 15 months) nine patients were alive and well. One patient (labeled STLMP) had metastatic liver disease 3 yrs after the primary surgery, at the last follow-up. Conclusions: 1) There is an overlap in using the terminologies as STUMP, AL, AL with low risk of recurrence, AL with low malignant potential. A designation of STUMP does convey a category of borderline malignancy to the gynecological surgeons. Most behave in a benign fashion and follow-up without adjuvant therapy is currently recommended. Critical evaluation of coagulative tumor necrosis is essential. Follow-up remains a challenge in our setting.

Complimentary role of FDG-PET imaging and skeletal scintigraphy in the evaluation of patients of prostate carcinoma.

Prostate cancer is one of the most common malignancies of elderly males. Management depends on the accurate estimation of disease both at initial diagnosis and in its subsequent course. In the present study, we evaluated the diagnostic utility of positron emission tomography with 18 F-fluorodeoxyglucose (FDG-PET) in patients having prostate cancer. The findings were compared with the results of bone scan (BS) for the detection of bone metastases. Sixteen patients (age range, 55-83 years) with confirmed diagnosis of prostate cancer were included in the prospective study. Three patients had undergone bilateral orchidectomy, 1 had hormonal therapy, 9 had undergone both, and 3 had no therapy. All the patients underwent wholebody BS and FDG-PET within 1 week. Interpretation of BS and FDG-PET were performed qualitatively. Osseous abnormalities detected by both methods were compared. Involvement of the disease in other sites as seen on FDG-PET was also noted. BS detected 197 osseous lesions, whereas FDG-PET could detect 97 (49%) bone lesions. However, in 3 patients without any prior therapeutic intervention, FDG-PET results were superior or equivalent to that of BS. FDG-PET also detected extensive involvement of the disease in the bone marrow in 4 patients, lymph node metastases at various sites in 8, liver metastases in 2, and lung metastases in 1 patient. FDG-PET could demonstrate less number of osseous metastases in comparison with BSs, but the results have to be interpreted in the background of prior treatment administered and the tumor biology of the lesion. It is evident that FDG-PET could detect the unknown soft tissue involvement of the disease with good sensitivity, which might play an important role in the management of prostate cancer. Overall, in the absence of novel PET tracers, both skeletal scintigraphy and FDG-PET imaging can play a complimentary role in the management of prostate cancer.

Diagnostic dilemma in an elderly woman with intractable ascites and elevated CA-125 level.

In patients with intractable ascites, careful consideration should be given to the patient's past history with emphasis on cardiac, liver and renal disorders. Ascitic fluid cytology indicating the presence of malignant cells should be unequivocal; cytology should be repeated before embarking on potentially toxic anti-cancer treatment in ambiguous cases. Elevated serum CA-125 levels should not be relied upon to make the diagnosis of ovarian/peritoneal carcinoma. We report a case of tricuspid stenosis with severe ascites in an elderly woman who was initially mis-diagnosed and treated as peritoneal/ovarian carcinoma.

Hypofractionated radiotherapy in carcinoma cervix IIIB: Tata Memorial Hospital experience.

PURPOSE OF THE STUDY: To analyze the role of hypofractionated radiotherapy in advanced carcinoma of cervix. BASIC PROCEDURE: Medical records of 62 women with advanced carcinoma cervix III3 treated during 1994-1996 were reviewed. Patients were treated with standard pelvic portals to a total dose of 39Gy in 13 fractions over 17 days followed by intracavitary brachytherapy. Forty-eight patients completed the planned treatment and were considered suitable for analysis of late reactions and survival. MAIN FINDINGS: The 5-year disease free survival was 59% and the overall survival was 50% at the mean follow up of 40 months. Twenty-one (44%) patients developed acute gastrointestinal toxicity of which 5 patients had grade III and one patient had grade IV reaction. Ten patients (21%) developed acute genitourinary complications, 13 patients (27%) had late rectal reactions and 10 patients (20%) had late bladder complications. Three patients had grade I, five had grade II and five had grade III late rectal toxicity. CONCLUSION: Survival in patients treated hypofractionated radiotherapy appears comparable to that of standard fractionation. The acute gastrointestinal and skin reactions were mainly grade I or grade II. Hypofractionated radiotherapy can certainly be considered in a select group of patients where the local disease is extensive and is unsuitable for conventional treatment.

Embryonal rhabdomyosarcoma of prostate in an adult--a diagnostic dilemma.

Embryonal rhabdomyosarcoma of the prostate is a rare. Highly malignant tumour. The median age of occurrence is five years, but sporadic cases have been reported in adults' To the best of our knowledge, till date, fewer than ten cases have been reported of which only two are above the age of sixty years. We report a case of embryonal rhabdomyosarcoma of prostate in a patient more than sixty years of age. If one is not aware of this entity, one can make a mistake in the diagnosis as well as treatment.

Primary carcinoma of fallopian tube--a case study.

Primary carcinoma of fallopian tube is a rare entity. We report an interesting case of primary carcinoma of fallopian tube with contralateral lymph node involvement. The clinicopathological findings and its management is presented.

Borderline epithelial tumours of the ovary--a retrospective analysis of 31 cases.

Thirty one cases of epithelial borderline tumours of the ovary recorded over a period of six years were reviewed. The incidence of borderline tumours was 6% in relation to ovarian epithelial malignancies, with serous and mucinous types comprising three fourth of the lesions. The serous tumours were bilateral in 39%, revealed surface growth in 17% and had peritoneal implants in 11% of cases. The mucinous tumours were bilateral in 11% and had associated pseudomyxoma peritonei in 22% of cases. Nuclear grade appeared to correlate with extraovarian spread and surface growth in the serous borderline tumours, but not in the mucinous borderline tumours. The endometrioid borderline tumours and mixed epithelial borderline tumours were rare lesions. Twenty one patients (68%) presented in Stage-la. Surface growth correlated with recurrences. The prognosis remained good in serous borderline tumours even in the presence of implants as these were non-invasive. The mean disease free survival was 43.03 months. There was no statistical difference in disease free survival of patients with and without implants.

The impact of cisplat based chemotherapy on advanced ovarian cancer.

Cisplatinum based chemotherapy has become the standard treatment for ovarian cancers due to its proved superiority over non-cisplat based regimes. However, the therapeutic impact of cisplat based regimes compared to cheaper non-cisplatinum based regimes is questionable when multiple variables such as residual disease, histologic type, grade are introduced. This report is a study of 110 Stage III ovarian cancer patients from 1985-89, with cisplat (n = 69) and non cisplat (n = 41) based chemotherapy. The results of both regimes with reference to the multiple variable factors are presented. We conclude that cisplat based regimes appear to be superior to non-cisplat based regimes except probably in poorly differentiated ovarian tumors where the results were similar with either regimen.

Superficial bladder cancer. A 10 year experience.

A total of 236 patients - 198 males and 38 females with superficial bladder cancer (stage A(TaT1)) were treated with transurethral resection of the tumours. Intravesical chemotherapy (84 patients) or immunotherapy (27 patients) was added in those patients considered to be at high risk of developing local recurrences or stage progression. The five and ten years survival in the single tumour group (117 patients) were 86 percent and 72.9 percent as compared to 72.5 percent and 70.7 percent respectively in the multiple tumour group (119 patients). The five and ten year survival rates for grade I tumours were 88.3 percent and 86 percent respectively, for grade II tumours 80.8 percent and 64 percent and for grade III tumours 56.9 percent and 46 percent respectively. The impact of tumour grade on survival was found to be independent of the number of tumours. The response rates to intravesical thiotepa was 54.9 percent mitomycin 60 percent and with BCG 71.5 percent. All the three reduced the local recurrence rates and increase the mean interval to recurrence but the stage progression rate was significantly lowered only with intravesical BCG. In our study, we have used the Danish strain of BCG available to us and have found it to yield response rates comparable to other centres using Tice or Pasteur strains.

Do we need to do comprehensive surgical staging in all cases of clinical early ovarian cancer?

Meticulous staging of ovarian cancer has so far been a prerequisite for treatment planning. However, more than 80% of patients operated by non-oncologists all over the world do not under go a complete staging. Recently there have been reports questioning the need for extensive staging from the point of cervical benefit. We have analysed our data of 64 stage ovarian cancer patients to see if clinical staging was adequate or relaparotomy with restaging is necessary. We conclude that though pathological staging is important for proper reporting of results and evaluation of treatment modalities, in the existing circumstances, a judicious use of clinical methods and taking available pathological factors into account, we can still produce comparable results with restricted use of relaparotomy.

Synchronous bilateral parotid metastases from renal cell carcinoma. A case report.

An unusual case of bilateral synchronous parotid metastases from renal cell carcinoma presenting seven years after nephrectomy is reported. The patient underwent bilateral superficial parotidectomy and is alive free of disease three and half years after the metastatectomy.